Although the process of collateral development following occlusion of a major artery has been studied extensively for a number of years, the mechanism of stimulation of collateral growth has yet to be clarified. Much of the conflict in the reported data can be related to the fact that the magnitude of the collateral resistance has been surmised from indirect evidence or measured in preparations that did not clearly separate collateral resistance from the resistance of the terminal microvascular bed. In the proposed experimental model, collateral and terminal artery thigh bed resistance will be measured simultaneously and separately and should provide a means for settling many of the controversies in this area. Other important questions to be answered include evaluations of the effects of chronic treatment with oral vasodilators, surgical sympathectomy and exercise on anatomical collateral and thigh bed resistance and functional constriction of collaterals and resistance vessels. The question of whether the beneficial effects of exercise on walking distance can be attributed to an improvement in hemodynamic factors will also be answered by the proposed experiments. Any detrimental or beneficial effects of venous occlusion on the chronic anatomical or functional response to arterial occlusion will be elucidated and the information should be of value in determining prognosis and in planning therapy for patients with the combined obstructions.